AMAG Pharmaceuticals, Inc. announced positive top-line results from a Phase III randomized, double-blind, non-inferiority clinical trial evaluating Feraheme (ferumoxytol) compared to Injectafer (ferric carboxymaltose injection) in approximately 2,000 adults with iron deficiency anemia (IDA). The study results demonstrated non-inferiority to Injectafer based on the primary composite endpoint of incidence of moderate-to-severe hypersensitivity reactions (including anaphylaxis) and moderate-to-severe hypotension. Additionally, the trial met secondary safety and efficacy endpoints, including the demonstration of superiority to Injectafer regarding mean improvement in hemoglobin per gram of iron administered from baseline to week 5.
"We believe this successful head-to-head, Phase III clinical trial marks an important milestone on our path toward gaining FDA approval for a broader Feraheme indication that includes all patients with iron deficiency anemia regardless of underlying cause," said Julie Krop, M.D., chief medical officer and senior vice president of clinical development and regulatory affairs at AMAG. "Approximately 4.5 million Americans have been diagnosed with IDA and suffer from its debilitating effects. We look forward to potentially bringing an alternative treatment option to these patients who have not been successfully treated with oral iron, including about 1.5 million women with IDA under the care of OB-GYNs, many of whom suffer from abnormal uterine bleeding."
Topline Results- Approximately 2,000 patients diagnosed with IDA regardless of underlying etiology were randomized in a 1:1 ratio into one of two treatment groups – 1.02 grams of Feraheme intravenous (IV) infusion (n=997) or 1.5 grams of Injectafer IV infusion (n=1,000). Feraheme met the study’s primary endpoint demonstrating non-inferiority to Injectafer (based on an NI margin of 2.64%) with respect to the percentage of patients who experienced moderate-to-severe hypersensitivity reactions (including anaphylaxis) and/or moderate-to-severe hypotension (Feraheme: 0.6%; Injectafer: 0.7%; treatment difference: -0.1%; 95% confidence interval: -0.80% to +0.61%; NI p=<0.0001). Feraheme also demonstrated non-inferiority to Injectafer for a secondary composite safety endpoint assessing incidence of moderate-to-severe hypersensitivity reactions (including anaphylaxis), serious cardiovascular events, and/or death (based on an NI margin of 3.6%) (Feraheme: 1.3%; Injectafer: 2.0%; treatment difference: -0.7%; 95% confidence interval: -1.81% to +0.42%; NI p=<0.0001).
Importantly, the study also showed a markedly greater incidence of hypophosphatemia (an exploratory endpoint defined by blood phosphorous of <0.6 mmol/L at week 2) in the patients dosed with Injectafer versus those dosed with Feraheme (Feraheme: 0.4% of patients; Injectafer: 38.6% of patients; treatment difference: -38.2%; 95% confidence interval: -41.31% to ?35.06%; superiority p-value p<.0001).
AMAG expects to file a supplemental new drug application (sNDA) with the FDA by mid-2017 to potentially broaden the use of Feraheme beyond the current chronic kidney disease (CKD) indication to include all adult IDA patients who have failed or cannot tolerate oral iron treatment, with an anticipated FDA decision in the first half of 2018.